We propose a series of interrelated studies on the pharmacokinetics and pharmacodynamics of furosemide and of the combination triamterene- hydrochlorothiazide. The metabolic profile, pattern of elimination of furosemide, and correlation with diuretic effect will be investigated in patients with varying degrees of renal insufficiency (including kidney transplant patients), patients with congestive heart failure, pulmonary edema and severe arterial hypertension. Studies will also determine the degree of intrasubject variability in furosemide absorption. Animal models (dog and rat) will be used to test the hypothesis that glucuronidation of furosemide occurs in the kidney. Studies will be carried our in whole animals as well as perfused kidney and liver preparation. Animal models will also be used to examine the effects of probenecid on the biliary excretion, glucuronide formation and renal excretion of furosemide and its metabolites. Measures of diuretic effect will be correlated with the rate and amount of unchanged drug in the urine. Studies with triamterene will determine the pharmacokinetics and pattern of drug metabolism for this drug in patients who have formed kidney stones which contain triamterene and its metabolites. We will test the hypothesis that stone formers may not as readily metabolize the poorly soluble traimterene to the much more soluble traimterene sulfate conjugate and compare the metabolic pattern with patients not forming stones. We will also determine the dose-response characteristics of traimterene in individuals rendered hypokalemic by a stable dose of hydrochlorothiazide. in this manner, we will attempt to evaluate the efficiacy of combination therapy of triamterene- hydrochlorothiazide and hope to predict the most reasonable dose ratio for these two diuretics.